Sustained Virological Suppression and Improvement of Adverse Events of Switching to Raltegravir Study

Phase 4

Completed

• Conditions: Quality of Life; HIV Infection; Adverse Drug Reaction
• Interventions: Drug: Raltegravir switch

• Registration Number: NCT01679964
• Lead Sponsor: Lin, Hsi-Hsun, M.D.

Brief Summary

Switching from the ritonavir-boosted protease inhibitor component to raltegravir in stable HIV-infected adult patients receiving combination therapy will demonstrate improved clinical tolerability or lipid profiles with sustained plasma virological response (\<50 copies/ml).

Detailed Description

A. Objectives To compare the treatment-emerged AEs and virological suppression after switch to raltegravir-based therapy in stable HIV-infected patients who receiving ritonavir-boosted protease inhibitor antiretroviral regimen

Primary endpoints:

1) The changes in overall incidence and severity of patient-reported clinical adverse events (based on "symptom distress module) after switch to raltegravir-based therapy.

Secondary endpoints:

1. The proportion of patients who are free of "virological failure" at week 48 after switch

2. The change from baseline in CD4 cell counts at week 48 after switch

3. The change in quality of life by assess the changes in the domain scores of MOS-HIV questionnaire at baseline and different study time points.

4. The changes in laboratory adverse event, e.g., the mean percent changes from baseline to 48 weeks in plasma lipid profile (total cholesterol, LDLCholesterol, HDL Cholesterol, triglycerides) after switch

5. The proportion of patients who are free of "treatment failure" at week 48 after switch

Safety endpoints

1. Incidence of adverse events

2. The proportion of patients with treatment-related grade 3 or 4 adverse events and laboratory abnormalities

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-08-30
• Study First Submitted QC: 2012-09-03
• Study First Posted: 2012-09-06
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-14
• Last Update Posted: 2016-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

• Patients who are infected with HIV-1
• Ages at least 20 years
• Patients are currently receiving a ritonavir-boosted PI-based regimen, including lopinavir, atazanavir, or darunavir, plus at least 2 antiretroviral agents (NRTIs)
• Patient complained of treatment-emerged clinical adverse events or abnormal lipid profile
• Patients with plasma HIV-1 viral RNA below 50 copies per ml for at least 6 months

Exclusion Criteria

• Patient with known history of contraindication or hypersensitivity to any component of the study regimen
• Patients with acute or decompensated chronic hepatitis in the previous 6 months
• Patients with chronic hepatitis and serum aminotransferase concentrations are more than 5 times the upper limit of the normal range
• Patients with renal insufficiency (patients need dialysis or have serum creatinine concentrations of more than twice the upper limit of the normal range
• Current alcohol or substance abuse (patients receiving methadone for the management of withdrawal symptoms due to substance abuse are allowed )
• Patients have failed previous regimens (prior to starting the current 2NRTI+PI/r regimen they are currently on)
• Patient's viral load have not been consistently <50 copies per ml for 6 months or longer.
• Patients initiated lipid lowering agents during the preceding 3 months
• Patients with any medical disorder or history of any illness which, in the opinion of the investigator, that the use of study medications is contraindicated or might confound the results of the study or pose additional risk in administering study drugs to the patient
• Pregnant, wish to become pregnant during the study period or breastfeeding women
• Patients who are lack of expectation to maintain assigned study medication during study period
• Patients who have received therapy with investigational drugs in the previous 3 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Raltegravir switch	Raltegravir switch	Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)

Primary Outcome Measures

Name	Time	Method
The proportion of patient-reported clinical adverse events	Week 4, 12-16, 28-32, 48	The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 4 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 12-16 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 28-32 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 48 weeks

Secondary Outcome Measures

Name	Time	Method
The proportion of patients who are free of "virological failure"	Week 4, 12-16, 28-32, 48	The proportion of patients who are free of "virological failure" at week 4 after switch, The proportion of patients who are free of "virological failure" at week 12-16 after switch, The proportion of patients who are free of "virological failure" at week 28-32 after switch, The proportion of patients who are free of "virological failure" at week 48 after switch
The change from baseline in CD4 cell counts	Week 4, 12-16, 28-32, 48	The change from baseline in CD4 cell counts at week 4 after switch, The change from baseline in CD4 cell counts at week 12-16 after switch, The change from baseline in CD4 cell counts at week 28-32 after switch, The change from baseline in CD4 cell counts at week 48 after switch
the change from baseline in life quality (based on the MOS-HIV questionnaire)	week 12-16, 48	The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 12-16 after switch, The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 48 after switch.
The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides)	Week 4, 12-16, 28-32, 48	The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks
The proportion of patients with treatment failure	Week 4, 12-16, 28-32, 48	The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks

Trial Locations

Locations (7)

Taipei City Hospital; 🇨🇳 Taipei, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Chang Gung Memorial Hospital at Linkou; 🇨🇳 Taoyuan, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

E-Da Hospital; 🇨🇳 Kaohsiung, Taiwan